It is proposed to continue study on the biochemical mechanisms in chemically induced neoplastic transformation and normal cellular differentiation using colorectal epithelium as a system. The focus will be on the process of replication and transcription. A concurrent attempt will be made to learn whether there is a connection between nuclear 6-8S DNA polymerases and abnormalities of DNA synthesis during the development of carcinoma, and to determine what changes have occurred in the gene regulatory control systems which now permit perpetual division of cancer cells. Since we believe that neoplastic growth is the manifestation of erroneous genetic controls, we would also like to identify chromosomal nonhistone proteins responsible for the regulation of gene expression. We plan to study the phosphorylation of nuclear nonhistone proteins and histones, specificities of nuclear phosphoprotein kinases, and the immunospecificity of nuclear antigens which arise during the process of chemical carcinogenesis. We feel that a multifaceted study of a carefully defined model system is the best approach currently available to study the nature of cancer.